Abstract
PurposePulmonary administration of dry drug powder is a considered promising strategy in the treatment of various lung diseases such as tuberculosis and is more effective than systemic medication. However, in the pre-clinical study phase, there is a lack of devices for effective delivery of dry powders to the lungs of small rodents. In this study, an administration device which utilizes Venturi effect to deliver dry powders to the lungs homogeneously was developed.MethodsA Venturi-effect administration device which synchronizes with breathes by use of a ventilator and aerosolizes the dry powders was created. Pulmonary distribution of inhalable dry powders prepared by spray-drying poly(lactic-co-glycolic) acid and an antituberculosis agent rifampicin and anti-tuberculosis effect of the powders on mycobacteria infected rats by administration with the Venturi-effect administration device and a conventional insufflation device were evaluated.ResultsHomogeneous distribution of the dry powders in the lung was achieved by the Venturi-effect administration device due to efficient and recurring aerosolization of loaded dry powders while synchronizing with breathes. Amount of rifampicin delivered to the lungs by the Venturi-effect administration device was three times higher than that by a conventional insufflation device, demonstrating three times greater antimycobacterial activity.ConclusionsThe Venturi-effect administration device aerosolized inhalable antituberculosis dry powders efficiently, achieved uniform pulmonary distribution, and aided the dry powders to exert antituberculosis activity on lung-residing mycobacteria.
Highlights
Inhalation of therapeutic agents is expected to be effective in the treatment of pulmonary diseases
It has been reported that microspheres with an aerodynamic diameter of 1–5 μm reach and deposit in the periphery of the lung efficiently, exerting optimum therapeutic activity [1] against lung diseases such as tuberculosis caused by Mycobacterium tuberculosis (MTB) [2,3,4]
When compressed air was supplied from duct 1 by a ventilator, the dry powder flowed through duct 2 due to the Venturi effect, which generated a negative pressure at the intersection, resulting in the formation of an aerosol insufflated from the tip of the device
Summary
Inhalation of therapeutic agents is expected to be effective in the treatment of pulmonary diseases. Pulmonary tuberculosis could be effectively treated via the pulmonary administration of antituberculosis agents encapsulated in microparticles, which are taken up by macrophages through phagocytosis. To administer inhalable microparticles to laboratory animals, nose-only inhalation chambers have been used as they breathe through the nose [6,7,8]. These instruments require a large amount of dry powders, and the exact amount of the drug inhaled cannot be determined [9]. Nose-only inhalation chambers are not practical for conducting efficacy tests of local acting and expensive pharmaceutical formulations
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